PROJECT SUMMARY The overarching goal of the Biospecimen/Pathology Core (BPC) is to facilitate translational research involving the acquisition and use of biological samples within the SPORE. To accomplish this, the Core will continue to offer a range of services for SPORE investigators and others in the Dana-Farber/Harvard Cancer Center (DF/HCC) breast cancer research community. These include 1) providing a tissue and blood repository; 2) collecting, storing, processing and analyzing tissue and blood from participants on SPORE clinical trials; and 3) providing readily accessible pathology and technical services, integrated with clinical data. In addition to standard pathology techniques, the BPC also offers access to state-of-the-art technologies, including cell-free DNA collection and analysis, multiplex immunofluorescence, automated imaging and genomic analyses. The BPC will centralize and prioritize access to biological samples for SPORE investigators, as well as support the larger DF/HCC breast cancer research community. Fresh tissue collection follows well-established protocols that are currently in place at three hospitals (Brigham and Women's Hospital [BWH], BW Faulkner Hospital [BWFH], and Massachusetts General Hospital [MGH]). Fixed tissue specimens are collected at all four hospitals (BWH, BWFH, MGH, and Beth Israel Deaconess Medical Center [BIDMC]). Blood collections take place at all outpatient locations. Specimen locations and linked clinical and pathologic annotations are maintained and distributions are tracked in caTissue. Requests for biospecimen use are reviewed and approved by a multidisciplinary DF/HCC Breast Data and Specimen Users Committee with representation across participating institutions. Pathology support is available at all stages of the research process. In this renewal application, we propose to maintain the same strong collection and distribution processes currently in place with added focus on collecting triple-negative breast cancer specimens, enhancing the formalin-fixed, paraffin-embedded (FFPE) research tissue archives, adding cell-free DNA methodologies, improving the molecular annotation of existing biospecimens and enhancing immuno-oncology expertise and capabilities. The BPC will have direct involvement in each of the proposed SPORE projects, overseeing the collection, storage, quality assessment and processing of clinical trial biopsies and blood samples, and supporting preclinical objectives. The Core will also work with investigators throughout the DF/HCC and the wider breast research communities, including projects supported through career development program awards and developmental projects.